中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2014年
4期
536-541
,共6页
乔进%窦志华%吴锋%孟国梁%陈惠%郑惠华
喬進%竇誌華%吳鋒%孟國樑%陳惠%鄭惠華
교진%두지화%오봉%맹국량%진혜%정혜화
灵芝多糖%二甲双胍%糖尿病大鼠%心肌纤维化%晚期糖基化终末产物%结缔组织生长因子%氧化应激
靈芝多糖%二甲雙胍%糖尿病大鼠%心肌纖維化%晚期糖基化終末產物%結締組織生長因子%氧化應激
령지다당%이갑쌍고%당뇨병대서%심기섬유화%만기당기화종말산물%결체조직생장인자%양화응격
ganoderma lucidum polyccharide%met-formin%diabetes mellitus rats%myocardial fibrosis%AGEs%CTGF%oxidative stress
目的:探讨灵芝多糖联合二甲双胍对2型糖尿病大鼠心肌纤维化的预防作用及其作用机制。方法 SD大鼠高脂饮食喂养4周后,腹腔注射链脲佐菌素(STZ)30 mg·kg-1建立2型糖尿病(type 2 diabetes mellitus,T2DM)模型。成模后将大鼠随机分为正常对照组、模型组、灵芝多糖组(灵芝多糖600 mg·kg-1)、二甲双胍组(二甲双胍600 mg·kg-1)及联合用药组(灵芝多糖300 mg · kg-1+二甲双胍300 mg · kg-1)。药物治疗12周末测量大鼠空腹血糖;饱和苦味酸-天狼猩红染色下观察心肌纤维化程度;荧光分光光度计法检测大鼠血清晚期糖基化终末产物( advanced glycosylation end products,AGEs)的含量;测量心肌过氧化氢酶( CAT)、谷胱甘肽过氧化物酶( GSH-Px )水平;免疫组化法和蛋白印迹法检测心肌组织AGEs及CTGF蛋白的表达。结果联合用药组可有效抑制心肌纤维化的病理进程,升高心肌组织CAT、GSH-Px水平及降低血清AGEs含量,减少心肌组织AGEs及CTGF的表达。结论灵芝多糖联合二甲双胍可能通过抑制心肌氧化应激,降低血清AGEs水平,以及下调心肌AGEs、CTGF的表达来预防心肌纤维化。
目的:探討靈芝多糖聯閤二甲雙胍對2型糖尿病大鼠心肌纖維化的預防作用及其作用機製。方法 SD大鼠高脂飲食餵養4週後,腹腔註射鏈脲佐菌素(STZ)30 mg·kg-1建立2型糖尿病(type 2 diabetes mellitus,T2DM)模型。成模後將大鼠隨機分為正常對照組、模型組、靈芝多糖組(靈芝多糖600 mg·kg-1)、二甲雙胍組(二甲雙胍600 mg·kg-1)及聯閤用藥組(靈芝多糖300 mg · kg-1+二甲雙胍300 mg · kg-1)。藥物治療12週末測量大鼠空腹血糖;飽和苦味痠-天狼猩紅染色下觀察心肌纖維化程度;熒光分光光度計法檢測大鼠血清晚期糖基化終末產物( advanced glycosylation end products,AGEs)的含量;測量心肌過氧化氫酶( CAT)、穀胱甘肽過氧化物酶( GSH-Px )水平;免疫組化法和蛋白印跡法檢測心肌組織AGEs及CTGF蛋白的錶達。結果聯閤用藥組可有效抑製心肌纖維化的病理進程,升高心肌組織CAT、GSH-Px水平及降低血清AGEs含量,減少心肌組織AGEs及CTGF的錶達。結論靈芝多糖聯閤二甲雙胍可能通過抑製心肌氧化應激,降低血清AGEs水平,以及下調心肌AGEs、CTGF的錶達來預防心肌纖維化。
목적:탐토령지다당연합이갑쌍고대2형당뇨병대서심기섬유화적예방작용급기작용궤제。방법 SD대서고지음식위양4주후,복강주사련뇨좌균소(STZ)30 mg·kg-1건립2형당뇨병(type 2 diabetes mellitus,T2DM)모형。성모후장대서수궤분위정상대조조、모형조、령지다당조(령지다당600 mg·kg-1)、이갑쌍고조(이갑쌍고600 mg·kg-1)급연합용약조(령지다당300 mg · kg-1+이갑쌍고300 mg · kg-1)。약물치료12주말측량대서공복혈당;포화고미산-천랑성홍염색하관찰심기섬유화정도;형광분광광도계법검측대서혈청만기당기화종말산물( advanced glycosylation end products,AGEs)적함량;측량심기과양화경매( CAT)、곡광감태과양화물매( GSH-Px )수평;면역조화법화단백인적법검측심기조직AGEs급CTGF단백적표체。결과연합용약조가유효억제심기섬유화적병리진정,승고심기조직CAT、GSH-Px수평급강저혈청AGEs함량,감소심기조직AGEs급CTGF적표체。결론령지다당연합이갑쌍고가능통과억제심기양화응격,강저혈청AGEs수평,이급하조심기AGEs、CTGF적표체래예방심기섬유화。
Aim To study the effects of ganoderma lu-cidum polysaccharides and metformin on myocardial fi-brosis of type 2 diabetic rats and its mechanism. Methods SD rats were fed with high fat diet for 4 weeks, and then were injected with streptozotocin (30mg·kg-1 ) to replicate type 2 diabetic model. The diabetic rats were randomized into normal control group,diabetes group, ganoderma lucidum polysaccha-rides group ( 600 mg · kg-1 ) , metformin group ( 600 mg·kg-1 ) , and combination group( ganoderma lucid-um polysaccharides 300 mg·kg-1 +metformin 300 mg ·kg-1 ) . After 12 weeks’ treatment,the levels of fast-ing serum glucose were determined and the extent of myocardial fibrosis was observed by Picro-sirius red staining. The contents of AGEs in serum were deter-mined by fluorescence spectrophotometer. The activities of CAT and GSH-Px in myocardium were detected. Im-munohistochemical method and Western blot were used to detect myocardial tissue AGEs and CTGF protein ex-pression. Results Combination group could repress patho-proceeding of myocardial fibrosis efficiently, im-prove the activity of CAT and GSH-Px in myocardium and lower the concentration of AGEs in serum, as well as reduce the expression of AGEs and CTGF in myo-cardium. Conclusions Ganoderma lucidum polysac-charides and metformin could prevent myocardial fibro-sis. The possible mechanism may be related to repress-ing oxidative stress of myocardium, lowering serum AGEs and down regulating AGEs and CTGF of myocar-dium.